1. Field
The present invention relates generally to blood filtration and to continuous renal replacement therapy (CRRT). More specifically, the invention relates to automatic control and optimization of citrate flow rate, and fluid exchange flow rates, during CRRT therapy.
2. Background
There are many continuous renal replacement therapies (CRRT) commonly used for treating patients suffering loss or impairment of natural renal functions. In a typical CRRT, blood is removed from a patient and pumped through an extracorporeal circuit that includes an artificial kidney. The artificial kidney contains a hemofilter or semi-permeable membrane. The blood is circulated along one surface of the membrane, and a dialysate fluid is circulated along the opposing surface. Through osmosis or differential pressure, the hemofilter allows migration of soluble waste and water from the blood across the membrane and into the dialysate solution. The filtered blood is then returned to the patient.
Generally, CRRT therapies remove water and waste solute at a slow and steady rate over long periods of time to ensure hemodynamic stability. In order maintain a constant total blood volume of a patient undergoing CRRT, a substitution fluid is introduced into the bloodstream in the extracorporeal circuit. Depending on the type of CRRT used, the substitution fluid may be introduced either upstream or downstream of the hemofilter. The composition of the substitution fluid, the composition of the dialysate, the flow rates of blood and dialysate, the pressure gradient across the membrane, and the composition of the membrane all contribute to the effectiveness of CRRT treatment.
Some of the more common CRRT methods in use today include ultrafiltration, hemodialysis, hemofiltration, and hemodiafiltration. Ultrafiltration describes any method that relies on movement of water from blood across a semi-permeable membrane, due to a pressure gradient across the membrane. Hemodialysis involves convective diffusion of solutes from blood across a semi-permeable membrane into a volume of dialysate flow. The dialysate is made to flow on one side of the membrane in a direction opposite the flow of blood on the other side of the membrane to maintain a concentration gradient across the membrane. Hemofiltration operates without a dialysate, and instead uses a positive hydrostatic pressure to drive water and solutes across a more porous membrane. Hemodiafiltration is a combination of hemodialysis and hemofiltration methods. In the literature, these therapies may be more specifically defined according to the patient access and return sites, and to fluid transfer characteristics, e.g. continuous venous-venous hemofiltration (CVVH), continuous venous-venous hemodialysis (CVVHD), continuous venous-venous hemodiafiltration (CVVHDF), high volume hemofiltration (HVHF), etc.
One problem common to all CRRT therapies is blood coagulation in the extracorporeal circuit, and primarily across the membrane within the artificial kidney. To prevent blood coagulation, an anticoagulant is typically added to the bloodstream in the extracorporeal circuit upstream of the hemofilter. Historically heparin has been used as a preferred anticoagulant, and more recently, citrate ions in the form of trisodium citrate have been proven effective in CRRT as an anticoagulant. A substitution fluid for use in hemofiltration that uses citrate as an anticoagulant, as well as additional background on citrate anticoagulation and CRRT therapies, are disclosed in U.S. Pat. No. 6,743,191, which is fully incorporated herein by reference.
One significant concern arising from the use of citrate as an anticoagulant is its effect on blood electrolyte levels. Citrate ions bond to positively charged electrolytes such as calcium and magnesium, thus, any passage of the citrate through the hemofilter and into the dialysate depletes these electrolytes from the bloodstream. If the proper electrolyte levels are not maintained during CRRT, in the worst case, hypocalcemia or hypomagnesemia may be induced in the patient and cause life-threatening complications.
Previous methodologies have been proposed for fixing citrate flow rate as a function of blood flow rate during CRRT. However, the results vary widely, and provide only general guidelines that do not necessarily optimize treatment in a specific case. Oudemans-van Straaten, H. M., “Guidelines for Anticoagulation in Continuous Venovenous Hemofiltration (CVVH),” recommends a citrate flow rate (CFR) of 35 mmol/h for a blood flow rate (BFR) of 200 ml/min. The “Monza protocol”, promoted by the Italian Association of Pediatric Hematology and Oncology (AIEOP) et al., recommends a CFR of 52.5 mmol/h for the same BFR. Strake, (no citation available) extrapolated to 200 ml/min BFR, recommends a CFR of 33.3 mmol/h. Mehta, R. L. et al., “Regional Citrate Anticoagulation for Continuous Arteriovenous Haemodialysis in Critically Ill Patients,” Kidney Int. 1990, Vol. 38(5), pp. 976-981, extrapolated to 200 ml/min BFR, recommends a CFR of 38.1 mmol/h. Kutsogiannis, D. J. et al., “Regional Citrate Anticoagulation in Continuous Venovenous Haemodiafiltration,” Am. J. Kidney Dis. 2000, Vol. 35(5), pp. 802-811, extrapolated to 200 ml/min BFR, recommends 40 mmol/h CFR. Palsson, R. et al., “Regional Citrate Anticoagulation in Continuous Venovenous Haemofiltration in Critically Ill Patients with a High Risk of Bleeding,” Kidney Int. 1999, Vol. 53, pp. 1991-1997, extrapolated to 200 ml/min BFR, recommends a CFR of 20.6 mmol/h. Tolwani, A. J. et al., “Simplified Citrate Anticoagulation for Continuous Renal Replacement Therapy,” Kidney Int. 2001, Vol. 60, pp. 370-374, extrapolated to 200 ml/min BFR, recommends a CFR of 28 mmol/h. Cointault, O. et al., “Regional Citrate Anticoagulation in Continuous Venovenous Haemodiafiltration Using Commercial Solutions,” Nephrol. Dial. Transplant., January 2004, Vol. 19(1), pp. 171-178, extrapolated to 200 ml/min BFR, recommends a CFR of 45.6 mmol/h. Taken as a whole, the available literature provides no consensus for optimizing regional citrate anticoagulation.
During administration of CRRT, regardless of CRRT type and protocol, multiple parameters in the blood filtration circuit must be maintained under strict control to ensure patient stability. Blood chemistry, blood and fluid flow rates, dialysate concentration, substitution fluid concentration, ultrafiltration rate, filter pressure drop, and fluid temperatures and pressures are some of the many parameters that must be carefully monitored and adjusted to ensure proper administration of the therapy. Depending on the particular blood chemistry and physical condition of the patient, the various flow rates and concentrations may need to be more finely adjusted. A source of citrate ions introduced in the system adds another dimension of complexity. What is needed is an expert system for controlling these parameters according to the needs of the individual patient.